Visceral sensory neurons of the vagus nerve innervate the major organ systems of the thorax and abdomen. Vagal sensory neurons transmit information concerning such diverse stimuli as blood pressure, gastric distension, bronchiolar irritation and blood oxygenation to their termini in the nucleus tractus solitarius (NTS) in the brainstem. Whereas much is known about the sensory receptors, the neuroanatomic pathways of the afferent neurons and about their reflexes, the neurotransmitters contained in vagal sensory nerves are not well characterized. We propose to study the neurotransmitter system(s) associated with these neurons. Our preliminary work showed the presence of the putative neurotransmitter substance P (SP) in vagal afferent neurons (including baro- and chemoreceptor afferent fibers), and showed SP receptors in the NTS. Other evidence exists for cholecystokinin (CCK) and serotonin (5-HT) as potential transmitters in vagal sensory neurons. Therefore, we will simultaneously study these 3 transmitter systems (1) to localize the primary source of the agent in the NTS to peripheral or central neurons, (2) to investigate the possibility of transmitter coexistence in the vagal sensory cell bodies of the nodose ganglion, (3) to learn which vagal sensory transmitters arise from which visceral organs, and (4) to correlate the neurotransmitter localization data with the presence of the appropriate transmitter receptors. Fluorescent tracer techniques will be combined with immunocytochemistry to determine both the central and peripheral pathways which contain a given neurotransmitter. Histochemical results will be verified and quantitated by lesions of the cell body region and assays of the transmitter content of the microdissected NTS. The neurotransmitter receptors in the NTS and associated with vagal sensory neurons will be localized with light microscopic autoradiography. These studies will provide information on the cellular neurobiology of transmitter systems in visceral sensory neurons, and in the NTS, the CNS site of integration of numerous visceral reflexes. This information may be useful in ultimately understanding derangements of the autonomic control of the cardiovascular, respiratory and gastro-intestinal systems. In addition, neurochemical characterization of these neurons may lead to advances in drug therapy of autonomic disorders.